Tatsuro Amano

Slowed oxygen uptake kinetics in hypoxia correlate with the transient peak and reduced spatial distribution of absolute skeletal muscle deoxygenation

•  What is the central question of the study? Does a transient overshoot in skeletal muscle deoxygenation (reflecting a kinetic mismatch of microvascular O2 delivery to consumption) and/or its spatial distribution slow the adjustment of oxidative energy provision at the onset of exercise? •  What is the main finding and its importance? Slowed oxidative energy provision at the onset of exercise was correlated with the transient skeletal muscle deoxygenation peak and the reduced spatial distribution, measured by quantitative near‐infrared spectroscopy. It was not correlated with a microvascular O2 delivery‐to‐consumption mismatch per se. This suggests that an absolute, rather than kinetic, mismatch of microvascular O2 delivery and consumption limits the kinetics of muscular oxidative energy provision, but only when muscle deoxygenation reaches some ‘critical’ level.

Sweating responses and the muscle metaboreflex under mildly hyperthermic conditions in sprinters and distance runners

To investigate the effects of different training methods on nonthermal sweating during activation of the muscle metaboreflex, we compared sweating responses during postexercise muscle occlusion in endurance runners, sprinters, and untrained men under mild hyperthermia (ambient temperature, 35°C; relative humidity, 50%). Ten endurance runners, nine sprinters, and ten untrained men (maximal oxygen uptakes: 57.5 ± 1.5, 49.3 ± 1.5, and 36.6 ± 1.6 ml·kg(-1)·min(-1), respectively; P < 0.05) performed an isometric handgrip exercise at 40% maximal voluntary contraction for 2 min, and then a pressure of 280 mmHg was applied to the forearm to occlude blood circulation for 2 min. The Δ change in mean arterial blood pressure between the resting level and the occlusion was significantly higher in sprinters than in untrained men (32.2 ± 4.4 vs. 17.3 ± 2.6 mmHg, respectively; P < 0.05); however, no difference was observed between distance runners and untrained men. The Δ mean sweating rate (averaged value of the forehead, chest, forearm, and thigh) during the occlusion was significantly higher in distance runners than in sprinters and untrained men (0.38 ± 0.07, 0.19 ± 0.03, and 0.11 ± 0.04 mg·cm(-2)·min(-1), respectively; P < 0.05) and did not differ between sprinters and untrained men. Our results suggest that the specificity of training modalities influences the sweating response during activation of the muscle metaboreflex. In addition, these results imply that a greater activation of the muscle metaboreflex does not cause a greater sweating response in sprinters.

Greater V̇O2peak is correlated with greater skeletal muscle deoxygenation amplitude and hemoglobin concentration within individual muscles during ramp‐incremental cycle exercise

It is axiomatic that greater aerobic fitness (V̇O2peak) derives from enhanced perfusive and diffusive O2 conductances across active muscles. However, it remains unknown how these conductances might be reflected by regional differences in fractional O2 extraction (i.e., deoxy [Hb+Mb] and tissue O2 saturation [StO2]) and diffusive O2 potential (i.e., total[Hb+Mb]) among muscles spatially heterogeneous in blood flow, fiber type, and recruitment (vastus lateralis, VL; rectus femoris, RF). Using quantitative time‐resolved near‐infrared spectroscopy during ramp cycling in 24 young participants (V̇2peak range: ~37.4–66.4 mL kg−1 min−1), we tested the hypotheses that (1) deoxy[Hb+Mb] and total[Hb+Mb] at V̇O2peak would be positively correlated with V̇O2peak in both VL and RF muscles; (2) the pattern of deoxygenation (the deoxy[Hb+Mb] slopes) during submaximal exercise would not differ among subjects differing in V̇O2peak. Peak deoxy [Hb+Mb] and StO2 correlated with V̇O2peak for both VL (r = 0.44 and −0.51) and RF (r = 0.49 and −0.49), whereas for total[Hb+Mb] this was true only for RF (r = 0.45). Baseline deoxy[Hb+Mb] and StO2 correlated with V̇O2peak only for RF (r = −0.50 and 0.54). In addition, the deoxy[Hb+Mb] slopes were not affected by aerobic fitness. In conclusion, while the pattern of deoxygenation (the deoxy[Hb+Mb] slopes) did not differ between fitness groups the capacity to deoxygenate [Hb+Mb] (index of maximal fractional O2 extraction) correlated significantly with V̇O2peak in both RF and VL muscles. However, only in the RF did total[Hb+Mb] (index of diffusive O2 potential) relate to fitness.

Changes in whole tissue heme concentration dissociates muscle deoxygenation from muscle oxygen extraction during passive head-up tilt

Skeletal muscle deoxygenated hemoglobin and myoglobin concentration ([HHb]), assessed by near-infrared spectroscopy (NIRS), is commonly used as a surrogate of regional O2 extraction (reflecting the O2 delivery-to-consumption ratio, Q̇/V̇o2). However, [HHb] change (Δ[HHb]) is also influenced by capillary-venous heme concentration, and/or small blood vessel volume (reflected in total heme; [THb]). We tested the hypotheses that Δ[HHb] is associated with O2 extraction, and insensitive to [THb], over a wide range of Q̇/V̇o2 elicited by passive head-up tilt (HUT; 10-min, 15° increments, between -10° and 75°). Steady-state common femoral artery blood flow (FBF) was measured by echo-Doppler, and time-resolved NIRS measured [HHb] and [THb] of vastus lateralis (VL) and gastrocnemius (GS) in 13 men. EMG confirmed muscles were inactive. During HUT in VL [HHb] increased linearly (57 ± 10 to 101 ± 16 μM; P < 0.05 above 15°) and was associated (r(2) ∼ 0.80) with the reduction in FBF (618 ± 75 ml/min at 0° to 268 ± 52 ml/min at 75°; P < 0.05 above 30°) and the increase in [THb] (228 ± 30 vs. 252 ± 32 μM; P < 0.05 above 15°). GS response was qualitatively similar to VL. However, there was wide variation within and among individuals, such that the overall limits of agreement between Δ[HHb] and ΔFBF ranged from -35 to +19% across both muscles. Neither knowledge of tissue O2 saturation nor vascular compliance could appropriately account for the Δ[HHb]-ΔFBF dissociation. Thus, under passive tilt, [HHb] is influenced by Q̇/V̇o2, as well as microvascular hematocrit and/or tissue blood vessel volume, complicating its use as a noninvasive surrogate for muscle microvascular O2 extraction.

Modulation of muscle metaboreceptor activation upon sweating and cutaneous vascular responses to rising core temperature in humans.

The present study investigated the role of muscle metaboreceptor activation on human thermoregulation by measuring core temperature thresholds and slopes for sweating and cutaneous vascular responses during passive heating associated with central and peripheral mechanisms. Six male and eight female subjects inserted their lower legs into hot water (43°C) while wearing a water perfusion suit on the upper body (34°C). One minute after immersion, an isometric handgrip exercise--40% of maximum voluntary contraction-was conducted for 1.5 min in both control and experimental conditions, while postexercise occlusion was performed in the experimental condition only for 9 min. The postexercise forearm occlusion during passive heating consistently stimulated muscle metaboreceptors, as implicated by significantly elevated mean arterial blood pressure throughout the experimental period (P <0.05). Stimulation of the forearm muscle metaboreceptors increased sweating and cutaneous vascular responses during passive heating, and was associated with significant reductions in esophageal temperature threshold of sweating and cutaneous vasodilation (Δ threshold, sweating: 0.33 ± 0.05 and 0.16 ± 0.04°C, cutaneous vascular conductance: 0.38 ± 0.08 and 0.16 ± 0.05°C for control and experimental groups, respectively, P < 0.05). The slopes of these responses were not different between the conditions. These results suggest that muscle metaboreceptor activation in the forearm accelerates sweating and cutaneous vasodilation during passive heating associated with a reduction in core temperature thresholds and may be related to central mechanisms controlling heat loss responses.

Changes in eccrine sweating on the glabrous skin of the palm and finger during isometric exercise

Aim:  The goals of this study were to investigate changes in the sweating and cutaneous vascular responses on the palm and the volar aspect of the index finger during sustained static exercise of increasing intensity and to determine whether the former can be attributed to altered sweat gland activity.

Sweating response to passive stretch of the calf muscle during activation of forearm muscle metaboreceptors in heated humans

Activation of muscle metaboreceptors and mechanoreceptors has been shown to independently influence the sweating response, while their integrative control effects remain unclear. We examined the sweating response when the two muscle receptors are concurrently activated in different limbs, as well as the blood pressure response. In total, 27 young males performed passive calf muscle stretches (muscle mechanoreceptor activation) for 30 s in a semisupine position with and without postisometric handgrip exercise muscle ischemia (PEMI, muscle metaboreceptor activation) at exercise intensities of 35 and 50% of maximum voluntary contraction (MVC) under hot conditions (ambient temperature, 35°C, relative humidity, 50%). Passive calf muscle stretching alone increased the mean sweating rate significantly on the forehead, chest, and thigh (SRmean) and mean arterial blood pressure (MAP), but not the heart rate (HR), from prestretching levels by 0.04 ± 0.01 mg·cm(2)·min(-1), 4.0 ± 1.3 mmHg (P < 0.05), and -1.0 ± 0.5 beats/min (P > 0.05), respectively. The SRmean and MAP during PEMI were significantly higher than those at rest. The passive calf muscle stretch during PEMI increased MAP significantly by 3.4 ± 1.0 and 2.0 ± 0.7 mmHg for 35 and 50% of MVC, respectively (P < 0.05), but not that of SRmean or HR at either exercise intensity. These results suggest that sweating and blood pressure responses to concurrent activation of the two muscle receptors in different limbs differ and that the influence of calf muscle mechanoreceptor activation alone on the sweating response disappears during forearm muscle metaboreceptor activation.

Sex differences in age-related changes on peripheral warm and cold innocuous thermal sensitivity

Cutaneous thermal sensitivity to a warm and cold stimulus was compared amongst 12 older (OF, 65.2±1.0year) and 29 younger (YF, 21.6±0.2years) female participants, and 17 older (OM, 66.2±1.5years) and 13 younger (YM, 21.2±0.4years) male participants to examine the effects of ageing and sex. In a neutral condition (27.5°C, 50% RH) during rest, warm and cold thermal sensitivity was measured on eight body regions (forehead, chest, back, forearm, hand, thigh, calf, and foot). Using the method of limits, a thermal stimulator was applied to the skin at an adapting temperature and either increased or decreased at a constant rate (0.3°C/s) until the participants detected the temperature with a push button. Thermal sensitivity declined with ageing to both a cold (older: 1468.6±744.7W/m(2), younger: 869.8±654.7W/m(2), p<0.001) and warm (older: 2127.0±1208.3W/m(2), younger: 1301.7±1055.2W/m(2), p<0.001) innocuous stimulus. YF and OF were more sensitive than YM and OM to both a warm and cold stimulus (p<0.05). There was no interaction between age and sex suggesting that whilst thermal sensitivity decreases with age the decrease is similar between the sexes (p>0.05). There was an interaction between temperatures, age and location and it seemed that cold thermal sensitivity was more homogenous for young and older participants however warm thermal sensitivity was more heterogeneous especially in the younger participants (p<0.05). Although the pattern was not similar between ages or sexes it was evident that the forehead was the most sensitive region to a warm and cold stimulus. Interestingly the decline in sensitivity observed with ageing occurred for all locations but was attenuated at the forehead in both males and females (p>0.05).

The effect of dietary nitrate supplementation on the spatial heterogeneity of quadriceps deoxygenation during heavy‐intensity cycling

This study investigated the influence of dietary inorganic nitrate (NO3−) supplementation on pulmonary O2 uptake ( V˙ O2) and muscle deoxyhemoglobin/myoglobin (i.e. deoxy [Hb + Mb]) kinetics during submaximal cycling exercise. In a randomized, placebo‐controlled, cross‐over study, eight healthy and physically active male subjects completed two step cycle tests at a work rate equivalent to 50% of the difference between the gas exchange threshold and peak V˙ O2 over separate 4‐day supplementation periods with NO3−‐rich (BR; providing 8.4 mmol NO3−∙day−1) and NO3−‐depleted (placebo; PLA) beetroot juice. Pulmonary V˙ O2 was measured breath‐by‐breath and time‐resolved near‐infrared spectroscopy was utilized to quantify absolute deoxy [Hb + Mb] and total [Hb + Mb] within the rectus femoris, vastus lateralis, and vastus medialis. There were no significant differences (P > 0.05) in the primary deoxy [Hb + Mb] mean response time or amplitude between the PLA and BR trials at each muscle site. BR significantly increased the mean (three‐site) end‐exercise deoxy [Hb + Mb] (PLA: 91 ± 9 vs. BR: 95 ± 12 μmol/L, P < 0.05), with a tendency to increase the mean (three‐site) area under the curve for total [Hb + Mb] responses (PLA: 3650 ± 1188 vs. BR: 4467 ± 1315 μmol/L sec−1, P = 0.08). The V˙ O2 slow component reduction after BR supplementation (PLA: 0.27 ± 0.07 vs. BR: 0.23 ± 0.08 L min−1, P = 0.07) correlated inversely with the mean increases in deoxy [Hb + Mb] and total [Hb + Mb] across the three muscle regions (r2 = 0.62 and 0.66, P < 0.05). Dietary NO3− supplementation increased O2 diffusive conductance across locomotor muscles in association with improved V˙ O2 dynamics during heavy‐intensity cycling transitions.

Mechanisms of nicotine-induced cutaneous vasodilation and sweating in young adults: roles for KCa, KATP, and KV channels, nitric oxide, and prostanoids

We evaluated the influence of K+ channels (i.e., Ca2+-activated K+ (KCa), ATP-sensitive K+ (KATP), and voltage-gated K+ (KV) channels) and key enzymes (nitric oxide synthase (NOS) and cyclooxygenase (COX)) on nicotine-induced cutaneous vasodilation and sweating. Using intradermal microdialysis, we evaluated forearm cutaneous vascular conductance (CVC) and sweat rate in 2 separate protocols. In protocol 1 (n = 10), 4 separate sites were infused with (i) lactated Ringer (Control), (ii) 50 mmol·L-1 tetraethylammonium (KCa channel blocker), (iii) 5 mmol·L-1 glybenclamide (KATP channel blocker), and (iv) 10 mmol·L-1 4-aminopyridine (KV channel blocker). In protocol 2 (n = 10), 4 sites were infused with (i) lactated Ringer (Control), (ii) 10 mmol·L-1 Nω-nitro-l-arginine (NOS inhibitor), (iii) 10 mmol·L-1 ketorolac (COX inhibitor), or (iv) a combination of NOS+COX inhibitors. At all sites, nicotine was infused in a dose-dependent manner (1.2, 3.6, 11, 33, and 100 mmol·L-1; each for 25 min). Nicotine-induced increase in CVC was attenuated by the KCa, KATP, and KV channel blockers, whereas nicotine-induced increase in sweat rate was reduced by the KCa and KV channel blockers (P ≤ 0.05). COX inhibitor augmented nicotine-induced increase in CVC (P ≤ 0.05), which was absent when NOS inhibitor was co-administered (P > 0.05). In addition, our secondrary experiment (n = 7) demonstrated that muscarinic receptor blockade with 58 μmol·L-1 atropine sulfate salt monohydrate abolished nicotine-induced increases in CVC (1.2-11 mmol·L-1) and sweating (all doses). We show that under a normothermic resting state: (i) KCa, KATP, and KV channels contribute to nicotinic cutaneous vasodilation, (ii) inhibition of COX augments nicotinic cutaneous vasodilation likely through NOS-dependent mechanism(s), and (iii) KCa and KV channels contribute to nicotinic sweating.